SMAD3

Protein SMAD3

Identifiers
SMAD family member 3
HUGO:SMAD3 hgnc_id:HGNC:6769 HGNC:6769 ENTREZ:4088 UNIPROT:P84022
HUGO:SMAD3, HGNC:6769, ENTREZ:4088, UNIPROT:P84022, GENECARDS:GC15P067358
HUGO:SMAD3
"MAD mothers against decapentaplegic homolog 3 (Drosophila)" MADH3 "SMAD mothers against DPP homolog 3 (Drosophila)"
HUGO:SMAD3 HGNC:6769 ENTREZ:4088 UNIPROT:P84022

Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / GROWTH_FACTORS_SIGNALING_PATHWAYS
EMT Senescence / EMT_REGULATORS
Innate Immunity / IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK

References
CASCADE:TGFB
PMID:11792802, PMID:12809600
The canonical TGFB signalling pathway involves phosphorylation of the carboxy-terminal serine residue of the internal modulator SMAD proteins, SMAD2 or SMAD3, by the activated receptors. This phosphorylation induces oligomerization of SMAD2 or SMAD3 with SMAD4, which is necessary for nuclear translocation.
PMID:11279127
Dominant-Negative Smad3 and Inhibitory Smad7 Expression Block TGF-??-induced ECM Promoter Activation in fibroblasts
COL1A2, COL3A1, COL6A1, COL6A3, and TIMP-1
PMID:12702545, PMID:8515656
Smad3 mediates transforming growth factor-beta-induced alpha-smooth muscle actin expression.
Protein level of SMAD3 and SMAD4 is upregulated after TGFB treatment
PMID:16179589
NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts.
On stimulation with TGF-beta1, Nox4 mRNA is dramatically upregulated.
Depletion of Nox4 but not Nox5 inhibits baseline and TGF-beta1 stimulation of Smad 2/3 phosphorylation
MACROPHAGE
NATURAL_KILLER
PMID:18768831
TGF-beta utilizes SMAD3 to inhibit CD16-mediated IFN-gamma production and antibody-dependent cellular cytotoxicity in human NK cells.
SMAD3 downstream of TGFB inhibits expression TBX21 (T-BET). TBX21 is involeved in IFNG gene activation.
PMID:16713975
TGF-?? signaling could target IFNG gene expression via TBX21 (TBET) and in a SMAD-dependent fashion that is independent of T-BET.
SMAD3 can directly interact with IFNG promoter.
PMID:21042762
Inhibition of TGF-?? signalinginduced phenotypic maturation of BM-DCs and human DCs and improved their abilities to produce IL-12 in a dose-dependent manner via SMADs.
PMID:22331441
Smad2/3 inhibited IFN-?? production by suppressing IRF3 transcriptional activity.
Smad2/3 somehow suppresses IRF3 phosphorylation in macrophages
Smad2 and Smad3 negatively regulate iNOS induction in macrophages by suppressing multiple steps in the IRF3-IFN-??-STAT1 pathway
TGF-?? exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes.
PMID:21614932

Modifications:
In compartment: INNATE_IMMUNE_CELL_Cytosol

SMAD3@INNATE_IMMUNE_CELL_Cytosol
SMAD3|pho@INNATE_IMMUNE_CELL_Cytosol

Participates in complexes:
In compartment: INNATE_IMMUNE_CELL_Cytosol

SMAD3|pho:SMAD4@INNATE_IMMUNE_CELL_Cytosol

Participates in reactions:
As Reactant or Product:

As Catalyser: